Body fluid homeostasis depends on reflexes which act to modulate the rate of renal water and sodium loss and on ingestive behaviors (i.e., thirst and salt appetite) that correct deficits. Although renal mechanisms can slow fluid loss, the restoration of vascular volume depends on the ingestion of water and solute (e.g., sodium). The maintenance of extra-cellular volume requires that the CNS receives and processes information about the status of body water and sodium. Several visceral sensory systems are known to provide this afferent input but there is only a very limited understanding about how this information is handled by the CNS. The present proposal builds upon our prior studies on the central processing of afferent signals involved in body fluid and cardiovascular homeostasis. Experiments using a rapid-onset model of sodium depletion accompanied by mild hypotension will focus on defining the role of serotonergic and cholecystokinergic mechanisms associated with the lateral parabrachial nucleus (LPBN) that we have implicated in the regulation of extracellular fluid volume. The proposed studies employing functional (behavioral), pharmacological, electrophysiological and neuroanatomical methods are designed to lead to converging experimental findings to increase our understanding of how the brain processes information necessary for maintaining body fluid and cardiovascular homeostasis. Such new information has relevance for the well-being of normal individuals exposed to physiological (exercise) and environmental (heat) challenges and for understanding mechanisms underlying pathological conditions related to fluid balance (e.g., hypertension; congestive heart failure; renal disease).